1. HIV integrase. The recent encouraging results from the application of a multiple target drug strategy for HIV suggests that the addition of a third target, the HIV integrase, might be even more effective in evading viral drug resistance through mutation. We have been engaged in a structural analysis of this enzyme and have previously reported the crystallization and structure determination of the catalytic core domain, residues 50-212. We have now crystallized this core domain in several different crystal forms that reveal more details about some of the residues that were disordered in the original structure. We have also prepared a variety of other fragments of the integrase in an effort to crystallize the core domain coupled to either or both of the remaining domains. Some encouraging results have been obtained but diffraction quality crystals have not yet been produced. 2. The HIV protease. We have examined the crystal structures of several complexes of the HIV protease complexed with several peptides that bind to the enzyme and inhibit its activity. The results are unusual in that there is cleavage of the octapeptide and apparent binding of the N-terminal pentapeptide, representing product inhibition of the enzyme. The structure of a tripeptide that is part of this octapeptide sequence has been determined.